A tissue model for quantitative studies on time course of healing, rate of healing, and cell proliferation after wounding.

The perforated true mesentery of the rat was exploited as a model for the quantitative study of connective tissue wound healing. Healing by closure was examined daily after the virtually-vessel-free mesentery had been perforated with a scalpel. Proliferation was quantitated in fibroblast- and mesothelial-like cells in spreads of mesentery at defined distances from the wound margin, by means of cytophotomeric Feulgen-DNA measurements and by mitotic counting. Proliferation was also estimated by specific DNA-activity in perforated and unperforated mesentery membranes. Mast-cell histamine was quantitated as an indicator of disturbed tissue homeostasis. In young rats, healing by closure started on day 4, and was complete on day 10. The maximum rate of healing occurred on days 5-7. Old animals showed essentially the same rate of healing as young ones but healing was significantly delayed. Sham-operated animals showed a moderate release of histamine and increased proliferation. Wounding caused additional release of histamine and was followed by increased proliferation after 48-96 h. With this novel procedure, the time course, the rate of healing, and the proliferation of cells at defined distances from the wound can be defined quantitatively. The technique may well prove valuable in the study of the interplay between proliferation and healing and in the study of the effect of local and systemic factors on connective tissue wound healing.